Serum samples from patients with chronic HBV infection were sequenced to determine the frequency of and to characterize the mutations in HBV genome. The findings were correlated with activity of liver disease, level of virus replication, and responsiveness to antiviral therapy. Studies in the past year showed that mutations in the HBV S gene can be induced by hepatitis B immunoglobulin and that S escape mutants may play a role in HBV reinfection post-liver transplant. Our current studies are focused on the effect of HBIG on changes in the pre-S and other regions of the HBV genome.